Mitochondria are key organelles for ATP production and apoptosis. Therefore, impairment of mitochondria can modulate or accelerate cancer progression. p32, originally identified as a pre-mRNA splicing factor SF2/ASF-associated protein, is localized predominantly in the mitochondrial matrix and involved in mitochondria respiration. Recently, p32 was implicated in apoptosis and resultantly cancer progression. However, little is known about the expression and function of p32 in human tumors including prostate cancer. Here, we investigated the expression of p32 in 148 prostate carcinoma tissues by immunohistochemistry and found a positive correlation of p32 expression to clinicopathological parameters including follow-up data. p32 is highly expressed in prostate tumor samples and its expression is significantly associated with the Gleason score, pathological stage and relapse. For localized cancers, high p32 is a strong and independent predictor of clinical recurrence in multivariate analysis (P = 0.01). In addition, p32 is overexpressed in the prostate cancer cell lines examined. The selective knockdown of p32 by RNA interference inhibits the growth of prostate cancer cell lines but not of a non-cancerous cell line. The p32 RNA interference decreases cyclin D1, increases p21 expression and causes a G1/S cell cycle arrest in prostate cancer cells. These data suggest that p32 is critical for prostate cancer cell proliferation and may be a novel marker of clinical progression in prostate cancer. (Cancer Sci 2011; 102: 639-647) p 32 (C1QBP ⁄ gC1qR ⁄ HABP1) was first isolated from a membrane preparation of Raji cells historically and was originally copurified with the pre-mRNA splicing factor SF2 ⁄ ASF in human HeLa cell.(1-3) p32 protein is a doughnutshaped trimer (4) that is primarily localized in the mitochondria, (1,(5)(6)(7) but has also been reported to be present at the cell surface (6,8) and in the nucleus (5,9,10) Human p32 has been reported to interact with a variety of molecules including human immunodeficiency virus Tat, complement 1q (C1q) and hyaluronic acids.(11) These results suggest that p32 may be a multifunctional chaperone protein.(12) Recently, it was reported that p32 was implicated in mediating the cellular apoptotic response.(13) ARF interacts with p32 and the interaction is critical in order for ARF to localize to the mitochondria and induce apoptosis. (14,15) It has also been proposed that p32 is a link to autophagy. (16,17) However, the role of p32 in mammalian cancer cells is unclear.Previously, we identified a Saccharomyces cerevisiae homologue of the human p32 gene, referred to as mam33, which was localized in the mitochondrial matrix. Disruption of the mam33 gene caused growth retardation and impairment of mitochondrial ATP synthesis. The growth impairment was restored by the introduction of human p32 cDNA, indicating that mam33 is a functional yeast counterpart of human p32. Taken together, both human p32 and yeast mam33 reside in the mitochondrial matrix and play an important role in ...

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Prekallikrein deficiency is a rare autosomal recessive disease not considered to be associated with a tendency for bleeding, despite marked prolongation of activated partial thromboplastin time. Currently, six kinds of mutations in the prekallikrein gene are known to be associated with prekallikrein deficiency. In this report, we describe a patient with idiopathic thrombocytopenic purpura who was recognized to have severe prekallikrein deficiency. Molecular analysis of the patient's prekallikrein gene showed a homozygous Trp499Stop nonsense mutation that has not been reported previously. The mutant allele is predicted to encode a truncated protein lacking half of the catalytic domain of prekallikrein, suggesting that the truncated protein causes prekallikrein deficiency in the patient.

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